The measurement of the confocal volume of a confocal three-dimensional micro-x-ray fluorescence(3D-XRF)setup is a key step in the field of confocal 3D-XRF analysis.With the development of x-ray facilities and optical ...The measurement of the confocal volume of a confocal three-dimensional micro-x-ray fluorescence(3D-XRF)setup is a key step in the field of confocal 3D-XRF analysis.With the development of x-ray facilities and optical devices,3D-XRF analysis with a micro confocal volume will create a great potential for 2D and 3D microstructural analysis and accurate quantitative analysis.However,the classic measurement method of scanning metal foils of a certain thickness leads to inaccuracy.A method for calibrating the confocal volume is proposed in this paper.The new method is based on the basic content of the textbook,and the theoretical results and the feasibility are given in detail for the 3D-XRF mono-chromatic x-ray condition and the poly-chromatic x-ray condition.We obtain a set of experimental confirmation using the poly-chromatic x-ray tube in the laboratory.It is proved that the sensitivity factor of the 3D-XRF can be directly and accurately obtained in a real calibration process.展开更多
Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.S...Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.展开更多
Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health,leading to reduced life expec-tancy,impaired energy homeostasis and increased health proble...Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health,leading to reduced life expec-tancy,impaired energy homeostasis and increased health problems.The p160 steroid receptor coactivator(SRC)gene family members have been suggested to be involved in energy homeostasis,but the impact of SRC-3 ablation on white and brown adipose tissue needs to be elucidated.In the current study,we collected in vivo data and carried out morphological studies on the effect of SRC-3 deficiency on white adipose tissue(WAT)and brown adipose tissue(BAT).Primary cells were cultured to investigate the differentiation ability of both adipocytes.Western blot was applied to detect the expression of master genes governing adipogenesis and thermogenesis.We observed that SRC-3^(–/–)mice were lean,with reduced WAT and decreased serum leptin levels,mainly due to the smaller white adipocyte size caused by impaired adipo-genesis,presented by decreased peroxisome proliferator activated receptor g(PPARg)expression.In the BAT,the lipid droplets decreased significantly in SRC-3^(–/–)mice as demonstrated by histological analysis and electron micro-scopic observation,which could be explained by enhanced thermogenesis.The expression of thermogenic marker gene PPARg coactivator 1αand uncoupling protein-1 increased in BAT of SRC-3^(–/–)mice,which proved our observations.Collectively,these results demonstrate that SRC-3 plays a key role in adipogenesis and energy expenditure.展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11675019 and 11875087).
文摘The measurement of the confocal volume of a confocal three-dimensional micro-x-ray fluorescence(3D-XRF)setup is a key step in the field of confocal 3D-XRF analysis.With the development of x-ray facilities and optical devices,3D-XRF analysis with a micro confocal volume will create a great potential for 2D and 3D microstructural analysis and accurate quantitative analysis.However,the classic measurement method of scanning metal foils of a certain thickness leads to inaccuracy.A method for calibrating the confocal volume is proposed in this paper.The new method is based on the basic content of the textbook,and the theoretical results and the feasibility are given in detail for the 3D-XRF mono-chromatic x-ray condition and the poly-chromatic x-ray condition.We obtain a set of experimental confirmation using the poly-chromatic x-ray tube in the laboratory.It is proved that the sensitivity factor of the 3D-XRF can be directly and accurately obtained in a real calibration process.
基金supported by the NSFC Distinguished Young Scholars Fund(82325010)the National Natural Science Foundation of China(82370874)+4 种基金the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212700)the Major Natural Science Project of the Scientific Research and Innovation Plan of Shanghai Municipal Commission of Education(2023ZKZD17)the Shanghai Research Center for Endocrine and Metabolic Diseases(2022ZZ01002)the Shanghai Key Discipline of Public Health Grants Award(GWVI-11.1-20)the Basic Scientific Research Project(General Cultivation Program)of Shanghai Sixth People’s Hospital(ynms202203).
文摘Background:Acute liver injury(ALI)requires rapid hepatic regeneration to avert fatal liver failure.As key mechanisms,systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process.Skeletal muscle,as a major metabolic organ system,undergoes significant remodeling during ALI.However,its specific regulatory contributions remain largely uncharacterized.Methods:Partial(2/3)hepatectomy and acetaminophen were used to induce ALI in male mice.RNA-sequencing(RNA-seq),assay for transposase-accessible chromatin by sequencing(ATAC-seq),chromatin immunoprecipitation,luciferase assay,Western blotting,TUNEL assay,immunohistochemistry,and phase separation assays were performed to reveal the transcriptional axis involved.Serum fibroblast growth factor binding protein 1(FGFBP1)protein levels in ALI patients were assessed via enzyme-linked immunosorbent assay.Results:Integrated analysis of RNA-seq and ATAC-seq following ALI identifies glucocorticoid(GC)signaling-mediated regulation of fibroblast growth factor 6(FGF6)in skeletal muscle metabolism.Muscle-specific knockdown of GC receptor(GR)exacerbates ALI and suppresses liver regeneration.Fgf6-knockout mice exhibited improved ALI and enhanced liver regeneration,with intramuscular injection of FGF6-neutralizing antibody rescuing the detrimental effects induced by GR knockdown.Further analysis of the FGF6 downstream target revealed that FGF6 regulates FGFBP1 expression through extracellular signal regulated kinase-activating transcription factor 3 signaling.Moreover,FGF6 regulates the heparin-dependent release kinetics of FGFBP1 by perturbing its liquid-liquid phase separation(LLPS)-driven condensate dynamics at the plasma membrane.Circulating FGFBP1 subsequently interacts with hepatic FGF5 through LLPS mechanisms to regulate liver regeneration.Conclusion:Our results demonstrate a molecular mechanism by which muscle-liver crosstalk can initiate and sustain liver regeneration via the FGF6-FGFBP1/FGF5 axis,providing a potential therapeutic target and treatment strategy for ALI.
基金supported by grants from the National Basic Research Program of China(No.2006CB503904)Natural Science Foundation of China(Grant Nos.30725037 and 30971385)Shanghai Committee for Science and Technology(No.07JC14042).
文摘Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health,leading to reduced life expec-tancy,impaired energy homeostasis and increased health problems.The p160 steroid receptor coactivator(SRC)gene family members have been suggested to be involved in energy homeostasis,but the impact of SRC-3 ablation on white and brown adipose tissue needs to be elucidated.In the current study,we collected in vivo data and carried out morphological studies on the effect of SRC-3 deficiency on white adipose tissue(WAT)and brown adipose tissue(BAT).Primary cells were cultured to investigate the differentiation ability of both adipocytes.Western blot was applied to detect the expression of master genes governing adipogenesis and thermogenesis.We observed that SRC-3^(–/–)mice were lean,with reduced WAT and decreased serum leptin levels,mainly due to the smaller white adipocyte size caused by impaired adipo-genesis,presented by decreased peroxisome proliferator activated receptor g(PPARg)expression.In the BAT,the lipid droplets decreased significantly in SRC-3^(–/–)mice as demonstrated by histological analysis and electron micro-scopic observation,which could be explained by enhanced thermogenesis.The expression of thermogenic marker gene PPARg coactivator 1αand uncoupling protein-1 increased in BAT of SRC-3^(–/–)mice,which proved our observations.Collectively,these results demonstrate that SRC-3 plays a key role in adipogenesis and energy expenditure.
